No reliable means of therapy exists to date for patients with advanced renal cell carcinoma (RCC). This proposal concerns the application of the transfer of cellular immunity by immune RNA (I-RNA) in a randomized clinical trial in patients with renal cell carcinoma. Prior animal studies performed in our laboratory, utilizing a syngeneic mouse tumor host system, have indicated that immunotherapy with syngeneic spleen cells incubated in vitro with specific I-RNA raised in guinea pigs prevented death from pulmonary metastases in mice after excision of the primary tumor. In addition, Phase I studies of patients with metastatic RCC using the treatment plan detailed in this proposal have been completed. Preliminary results have demonstrated the following: 1) The I-RNA treated syngeneic lymphocyte infusions are well tolerated. 2) In vitro parameters of host anti-tumor response do reflect increased specific cell mediated cytotoxicity (CMC) against tissue-type specific tumor associated antigens after in vivo treatment. 3) There is no evidence of tumor growth acceleration after treatment. 4) Objective response of tumor regression has been observed in some patients after treatment. The proposed clinical study will be modeled on our experimental systems. Patients with Stage II RCC with extension into the inferior vena cava, Stage III RCC with positive regional lymph nodes, or Stage IV tumor with measurable disease in a prospective randomized trial will receive immune RNA therapy or standard therapy beginning approximately three weeks after excision of the primary tumor. I-RNA will be extracted from the lymphoid tissues of guinea pigs immunized against the patient's own tumor and will be incubated in vitro with the patient's peripheral blood lymphocytes. These autologus lymphocytes will then be returned to the patient intravenously after incubation. Correlation between in vitro parameters of tumor specific immunity and the patient's tumor-free survival will be sought utilizing tests for tumor specific CMC, complement dependent cytotoxicity, antibody dependent CMC and natural killer cell activity.